Cooling Plus Best Medical Treatment Versus Best Medical Treatment Alone for Acute Ischaemic Stroke

NCT ID: NCT01833312

Last Updated: 2019-10-02

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 98 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-07-31
• Study Completion Date: 2018-07-31

Brief Summary

The purpose of this study is to determine if systemic cooling to a target temperature of 34 to 35°C, started within 6 hours of symptom onset and maintained for 12 hours, improves functional outcome at 3 months in patients with acute ischaemic stroke.

Conditions

Acute Ischemic Stroke

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Hypothermia

Best medical treatment + hypothermia 34-35°C for 24h

Group Type: EXPERIMENTAL

Hypothermia

Intervention Type: DEVICE

In patients randomised to therapeutic hypothermia, induction of cooling will be started by infusion of 4°C isotone saline or Ringer's lactate administered over a period of 30 to 60 minutes. A body temperature between 34.0 and 35.0°C will be targeted. Body temperature will be monitored through bladder or rectal thermal probes, and cooling procedures will be adapted to keep body temperature as close as possible to the target. Maintenance of body temperature in the target range will be performed with a surface or endovascular cooling device. After a cooling period of 24h, controlled rewarming to 36°C with a rate of 0.2°C/h will be started. After 36°C have been reached, the device will be disconnected.

Buspirone

Intervention Type: DRUG

anti-shivering treatment

Pethidine

Intervention Type: DRUG

anti-shivering treatment

Control

Best medical treatment

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Hypothermia

In patients randomised to therapeutic hypothermia, induction of cooling will be started by infusion of 4°C isotone saline or Ringer's lactate administered over a period of 30 to 60 minutes. A body temperature between 34.0 and 35.0°C will be targeted. Body temperature will be monitored through bladder or rectal thermal probes, and cooling procedures will be adapted to keep body temperature as close as possible to the target. Maintenance of body temperature in the target range will be performed with a surface or endovascular cooling device. After a cooling period of 24h, controlled rewarming to 36°C with a rate of 0.2°C/h will be started. After 36°C have been reached, the device will be disconnected.

Intervention Type: DEVICE

Buspirone

anti-shivering treatment

Intervention Type: DRUG

Pethidine

anti-shivering treatment

Intervention Type: DRUG

Other Intervention Names

EMCOOLS Brain.Pad; Arctic Sun and ArcticGel Pads; CritiCool and CureWrap 3500; Zoll intravascular temperature management system

Eligibility Criteria

Inclusion Criteria

• Written informed consent obtained from the patient or his/her legally acceptable representative or under such other arrangements as may be legally established in participating countries
• Patients of both sexes aged ≥18 years
• Estimated body weight of 50 up to and including 120kg
• Diagnosis of acute ischaemic stroke
• Possibility to start therapeutic hypothermia within 6 hours after onset of stroke
• Possibility to start therapeutic hypothermia within 150 minutes after start of alteplase administration in patients receiving thrombolysis at the trial site or within 150 minutes after start of endovascular treatment, if this is later
• Possibility to start therapeutic hypothermia within 150 minutes after admission to trial site in patients not receiving thrombolysis or in patients who have received thrombolysis at a different site
• mRS score ≤2 prior to onset of stroke
• NIHSS score ≥6
• GCS motor response subscale score ≥5

Exclusion Criteria

• Use of monoamineoxidase inhibitors in the 14 days prior to screening
• Current use of medication interacting with pethidine or buspirone, i.e., ritonavir, phenytoin, cimetidine, phenothiazines, opioids and partial opioid agonists (e.g., pentazocine, nalbuphine, buprenorphine)
• Acute alcohol intoxication
• Opioid addiction
• Nursing mother or pregnant woman, as verified by a positive urine pregnancy test in females of childbearing potential
• Known hypersensitivity to the IMPs or any of their formulation ingredients
• Patient who is imprisoned or is lawfully kept in an institution
• Employee or direct relative of an employee of the CRO (if applicable), the department of the investigator, or the sponsor
• Participation in an interventional clinical trial within the last 4 weeks, or be under the exclusion period from another trial
• Prior participation in this trial
• Any acutely life-threatening conditions other than acute ischaemic stroke
• Rapidly resolving stroke symptoms
• Evidence from CT or MRI of intracranial haemorrhage or tumour or encephalitis or any diagnosis likely to cause the present symptoms other than acute ischaemic stroke. Haemorrhagic transformation of the infarct is not an exclusion criterion, except when there is a parenchymal haematoma covering more than 30% of the infarcted area, with significant space-occupying effect, or when there is a bleeding remote from the infarcted area
• Known convulsive disorder, acute closed angle glaucoma, myasthenia gravis
• SPO2 <94% (as measured by pulse oximetry) under nasal oxygen administration
• Other severe respiratory disorder
• Bradycardia (<40 bpm)
• Severe cardiac failure, defined as NYHA classification ≥III
• Myocardial infarction or angina pectoris in the 3 months prior to screening
• Vasospastic disorders (e.g., Raynaud's disease)
• Haematological dyscrasia (e.g., sickle cell disease, cryoglobulinaemia)
• Known platelet count <100,000/mm3
• Known INR >1.7
• Skin damage (e.g., inflammation, burns, injuries, ulcerations, hives, rash) at the sites intended to be used for cooling
• Clinical diagnosis of sepsis
• Known severe hepatic impairment (serum ALAT and/or ASAT >3 times ULN)
• Known renal impairment (serum creatinine >2mg/100ml)
• Addison's disease
• Any other condition that may interfere with, or be aggravated by, therapeutic hypothermia
• Any condition that is thought to reduce the compliance to cooperate with the trial procedures

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Erlangen-Nürnberg Medical School

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Stefan Schwab, Prof

Role: STUDY_CHAIR

University of Erlangen-Nürnberg

Locations

Department of Neurology, University Hospital Erlangen

Erlangen, , Germany

Countries

Germany

References

Winkel P, Bath PM, Gluud C, Lindschou J, van der Worp HB, Macleod MR, Szabo I, Durand-Zaleski I, Schwab S; EuroHYP-1 trial investigators. Statistical analysis plan for the EuroHYP-1 trial: European multicentre, randomised, phase III clinical trial of the therapeutic hypothermia plus best medical treatment versus best medical treatment alone for acute ischaemic stroke. Trials. 2017 Nov 29;18(1):573. doi: 10.1186/s13063-017-2302-z.

Reference Type: DERIVED

PMID: 29187242 (View on PubMed)

van der Worp HB, Macleod MR, Bath PM, Demotes J, Durand-Zaleski I, Gebhardt B, Gluud C, Kollmar R, Krieger DW, Lees KR, Molina C, Montaner J, Roine RO, Petersson J, Staykov D, Szabo I, Wardlaw JM, Schwab S; EuroHYP-1 investigators. EuroHYP-1: European multicenter, randomized, phase III clinical trial of therapeutic hypothermia plus best medical treatment vs. best medical treatment alone for acute ischemic stroke. Int J Stroke. 2014 Jul;9(5):642-5. doi: 10.1111/ijs.12294. Epub 2014 May 15.

Reference Type: DERIVED

PMID: 24828363 (View on PubMed)

Other Identifiers

EuroHYP-1

Identifier Type: -

Identifier Source: org_study_id